Substituting peptide linkages which are susceptible to enzymatic cleavage with linkages which are resistant to such cleavage is one way of altering the activity of polypeptide hormones. Such selective changes might allow one to pinpoint the positions in the polypeptide chain which are responsible for binding and/or biological activity. These analogs might conceivably possess antagonist activity. The class of compounds known as pseudodipeptides are those compounds in which the amide linkage has been replaced by a thioether. Some of these compounds were synthesized by Yankeelov, and coworkers (J. Org. Chem., 43, 1623 (1978)), who suggested that they might have a backbone conformation similar to that of the peptide analog while being resistant to hydrolysis. We have started a project of synthesis of a number of these thioethers with the object of incorporating them in selective spots in the epidermal growth factor molecule. Thus far, three pseudodipeptides, as well as diasteriomers of two of them have been prepared and characterized.